Efficacy and safety of GLP-1 receptor agonists in metabolic dysfunction-associated steatohepatitis: A systematic review and meta-analysis of randomized controlled trials

Background Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disorder that increases the risk of cirrhosis and liver-related death. Despite its growing prevalence, effective pharmacological treatments remain limited. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as potential agents capable of improving liver histology in patients with MASH. Objective This study aimed to evaluate the efficacy and safety of GLP-1 receptor agonists in promoting histological resolution of MASH and improving liver fibrosis in adults with biopsy-confirmed disease. Methods We systematically searched PubMed, Embase, Cochrane CENTRAL, and Scopus from inception to 27 June 2025 for randomized controlled trials comparing GLP-1 receptor agonists with placebo in adults with biopsy-proven MASH. The primary endpoint was MASH resolution without fibrosis progression; secondary endpoints were ≥1-stage fibrosis improvement and any adverse events. Study quality was assessed using the Cochrane Risk of Bias 2.0 tool. Pooled risk ratios (RRs) were estimated using a random-effects model. Results Three RCTs with a total of 1,172 participants were included. Treatment with GLP-1RAs significantly increased the likelihood of MASH resolution without fibrosis progression (RR = 2.04; 95% CI: 1.53–2.72; I 2 = 19%). GLP-1RAs also improved fibrosis without worsening of MASH (RR = 1.53; 95% CI: 1.24–1.89; I 2 = 0%). A modest rise in overall adverse events was observed (RR = 1.08; 95% CI: 1.02–1.14; I 2 = 9%), primarily reflecting mild to moderate gastrointestinal symptoms. Conclusion GLP-1 receptor agonists, particularly semaglutide and liraglutide, significantly enhance histologic outcomes in patients with biopsy-confirmed MASH while maintaining a favorable safety profile. These findings highlight the potential of GLP-1RAs as disease-modifying agents for MASH, especially in individuals with metabolic comorbidities.